BIOMATERIALS
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2021
·
IF 12.479
Si-Yuan Peng,Xin-Hua Liu,Qi-Wen Chen,Yun-Jian Yu,Miao-Deng Liu,Xian-Zheng Zhang
The overexpression of glutathione (GSH) in cancer cells has long been regarded as the primary obstacle for reactive oxygen species (ROS)-involved anti-tumor therapies. To solve this issue, a ferric ion and selenite-codoped calcium phosphate (Fe/Se–CaP) nanohybrid here is fabricated to catabolize endogenous GSH, instead of directly deleting it, to trigger a ROS storm for tumor suppression. The selenite component in Fe/Se–CaP can catabolize GSH to superoxide anion (O 2 •− ) and hydroxyl radicals (•OH) via cascade catalytic reactions , elevating oxidative stress while destroying antioxidant system. The doped Fe can further catalyze the soaring hydrogen peroxide (H 2 O 2 ) originated from O 2 •− to •OH via Fenton reactions. Collectively, Fe/Se–CaP mediated self-augmented catabolism dynamic therapy finally induces apoptosis of cancer cells owing to the significant rise of ROS and, combined with CaP adjuvant, evokes adaptive immune responses to suppress tumor progression, providing an innovative train of thought for ROS-involved anti-tumor therapies.
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Frontiers in Cell and Developmental Biology
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2022
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IF 6.081
Deng Changping,Hu Fabiao,Zhao Zhangting,Zhou Yiwen,Liu Yuping,Zhang Tong,Li Shihui,Zheng Wenyun,Zhang Wenliang,Wang Tianwen,Ma Xingyuan
Quantitative analysis and regulating gene expression in cancer cells is an innovative method to study key genes in tumors, which conduces to analyze the biological function of the specific gene. In this study, we found the expression levels of Survivin protein (BIRC5) and P-glycoprotein (MDR1) in MCF-7/doxorubicin (DOX) cells (drug-resistant cells) were significantly higher than MCF-7 cells (wild-type cells). In order to explore the specific functions of BIRC5 gene in multi-drug resistance (MDR), a CRISPR/Cas9-mediated knocking-in tetracycline (Tet)-off regulatory system cell line was established, which enabled us to regulate the expression levels of Survivin quantitatively (clone 8 named MCF-7/Survivin was selected for further studies). Subsequently, the determination results of doxycycline-induced DOX efflux in MCF-7/Survivin cells implied that Survivin expression level was opposite to DOX accumulation in the cells. For example, when Survivin expression was down-regulated, DOX accumulation inside the MCF-7/Survivin cells was up-regulated, inducing strong apoptosis of cells (reversal index 118.07) by weakening the release of intracellular drug from MCF-7/Survivin cells. Also, down-regulation of Survivin resulted in reduced phosphorylation of PI3K, Akt, and mTOR in MCF-7/Survivin cells and significantly decreased P-gp expression. Previous studies had shown that PI3K/Akt/mTOR could regulate P-gp expression. Therefore, we speculated that Survivin might affect the expression of P-gp through PI3K/Akt/mTOR pathway. In summary, this quantitative method is not only valuable for studying the gene itself, but also can better analyze the biological phenomena related to it.
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Nano Energy
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2021
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IF 17.881
Shengying Cai,Changshun Xu,Danfeng Jiang,Meiling Yuan,Qingwen Zhang,Zhaoling Li,Yi Wang
Developing wearable and noninvasive electrochemical devices for glucose monitoring is desirable for diabetes diagnostics and management. However, the adoptions are restricted by their poor reliability due to diluted glucose densities in commonly-used body fluids while lack of highly sensitive electrodes. Graphene fiber fabric, which is macroscopically paper-like and assembled by wet-fused graphene fibers, provides excellent electrical and mechanical properties as well as penetration paths for liquids, showing great potentials for electrochemical monitoring . Additionally, the graphene fiber fabric as a sensing patch provides excellent air-permeability which is necessary for wearing comfort but has rarely been addressed. As a result, the Prussian blue-decorated graphene fiber fabric exhibits a high electrochemical sensitivity to hydrogen peroxide (7298.7 μA mM −1 cm −2 ). After being modified by glucose oxidase and chitosan, it delivers both high selectivity and electrochemical sensitivity to glucose (1539.53 μA mM −1 cm −2 in the concentration range of 2–220 μM, and 948.48 μA mM −1 cm −2 in the concentration range of 220–650 μM). We ascribe these performances to high-speed transfer paths for electrons and electrolytes in resultant electrodes. Additionally, the spontaneous absorption of body liquids by graphene fiber fabric after deposition of hydrophilic Prussian blue improves the utilization of active materials. Finally, the graphene fiber fabric used as a dry sensing patch was applied on human skin for the in vivo noninvasive glucose monitoring with the reverse iontophoresis (RI) technology, which showed good correlation to glucose levels measured by a commercial finger-prick glucometer.
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JOURNAL OF DRUG TARGETING
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2021
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IF 5.121
Chunjing Guo,Yanguo Su,Bingjie Wang,Qiang Chen,Huimin Guo,Ming Kong,Daquan Chen
With the increasing number of oncology patients and the use of chemotherapeutic agents, tumour multidrug resistance is becoming more and more prevalent. The search for new tumour treatment strategies to overcome tumour multidrug resistance is urgent. In this study, we designed GSH and ROS dual-responsive tumour-associated macrophages (TAMs)-targeted nanoparticles (NPs) for the co-delivery of the clinical first-line anti-breast cancer chemotherapy drug paclitaxel (PTX) and baicalin (Bai), which re-educates TAMs to alter their phenotype. We synthesised oligohyaluronic acid-mannose-folic acid (oHA-Man-FA, HMF) and astragalus polysaccharide-dithiodipropionic acid-paeoniflorol (APS-S-Pae, ASP), two hybrid materials that can self-assemble in water to form hybrid nanoparticles (HP-NPs) co-loaded with paclitaxel and baicalin (HP-NPs@PTX/Bai). The experimental results show that our designed hybrid nanoparticles can be specifically released in the tumour microenvironment and deliver the antitumor drug PTX as well as Bai, which reshapes the phenotype of TAMs, to the tumour site. The hybrid nanoparticles not only effectively re-educated TAMs from M2 TAM to M1 TAM, but also ameliorated the cytotoxic side effects caused by free PTX and provided better tumour suppression than free PTX and HP.
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JOURNAL OF COLLOID AND INTERFACE SCIENCE
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2021
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IF 8.128
Huiping Dang,Youliang Tian,Quan Cheng,Changchang Teng,Kai Xie,Lifeng Yan
It is essential to develop novel multifunctional and easily synthesized stable NIR-II fluorescent probes to guide photothermal therapy for tumors. Here, we propose a new strategy to construct boron dipyrromethene (BODIPY) J-aggregates by intermolecular hydrogen bonding (H-bond) and π-π stacking interactions to achieve fluorescence emission in the second near-infrared window (NIR-II, 1000–1700 nm). A novel meso -benzamide galactose hexanoate-BODIPY (Gal-OH-BDP) amphiphilic small molecular dye was synthesized and it formed nanoparticles spontaneously in aqueous solution with a maximum emission wavelength near 1060 nm, which works as a smart nanomedicine for targeting NIR-II imaging-guided photothermal therapy (PTT) of hepatocellular carcinoma. Galactose not only provided hydrogen bonds to regulate the aggregation pattern of the molecules but also effectively targeted hepatocellular carcinoma cells and promoted the formation of well-dispersed nanoparticles of dye molecules due to their hydrophilicity . Moreover, due to high photothermal conversion efficiency (PCE = 55%), Gal-OH-BDP NPs achieve galactose-targeted NIR-II imaging and PTT, which is important for the precise diagnosis and treatment of tumors ( Scheme 1 ). In the present research work, H-bond was introduced for the first time into BODIPY for building J-aggregates to achieve the NIR-II fluorescence.
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2021
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IF 5.279
Duo Liang,Wentao Su,Xue Zhao,Jiaxuan Li,Zheng Hua,Song Miao,Mingqian Tan
Improving the stability of fucoxanthin in the gastrointestinal tract is an important approach to enhance its oral bioavailability. The study proposed a new microfluidic device allowing for the synthesis of a structurally well-defined nanoscale delivery system with a uniform size for encapsulation and colon-target release of fucoxanthin. The rapid mixing in the microfluidic channel ensured that the mixing time was shorter than the aggregation time, thus realizing the controllable control of the coprecipitation of fucoxanthin and shellac polymer. In vitro digestion tests showed that a pH stimulus-responsive release of fucoxanthin from FX/SH NPs was observed under alkaline pH conditions. The fluorescence colocalization imaging indicated that FX/SH NPs did not affect the intestine function and had a protective effect on Caco-2 cells damaged by H2O2 by enhancing their antioxidant capacity. Overall, this work illustrated the promise of using a microfluidic approach to fabricate the biomimetic nanodelivery system for better biocompatibility and targeting efficacy.
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DRUG DELIVERY
·
2021
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IF 6.419
Wenwen Shen,Shuke Ge,Xiaoyao Liu,Qi Yu,Xue Jiang,Qian Wu,YuChen Tian,Yu Gao,Ying Liu,Chao Wu
In this study, we prepared a folic acid-functionalized SMMC-7721 liver cancer cell membrane (CM)-encapsulated paclitaxel nanocrystals system (FCPN) for hepatoma treatment. Transmission electron microscopy (TEM) characterization showed that FCPN was irregular spherical shapes with a particle size larger than 200 nm and a coated thickness of approximately 20 nm. In an in vitro release experiment, FCPN indicated a slowly release effect of paclitaxel (PTX). Cell experiments demonstrated that FCPN was taken up by SMMC-7721 cells and significantly inhibited the proliferation of SMMC-7721 cells, which illustrated that FCPN had good targeting ability compared with PN and CPN. According to the results of in vivo animal experiments, FCPN significantly inhibited tumor growth. Tissue distribution experiments proved that FCPN could accumulate significantly in tumor tissues, which further explained why FCPN had good targeting ability. These results clearly suggested that folate-functionalized homotypic CM bionic nanosystems might represent a very valuable method for liver cancer treatment in the future.
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NEW JOURNAL OF CHEMISTRY
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2021
·Vol. 45
·期 40
·19011-19018
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IF 3.591
Qiuying Song,Bo Zhou,Dongyu Zhang,Haijun Chi,Hongmin Jia,Peixun Zhu,Zhiqiang Zhang,Qingtao Meng,Run Zhang
The development of well-designed fluorescence probes for the monitoring of redox homeostasis in biosystems has attracted significant research interest owing to their non-invasive and real-time detection capability in vivo. In this work, a reversible near-infrared (NIR) fluorescence probe (XC) was designed and synthesized for the monitoring of HSO3−/H2O2-regulated cycles in vivo. The XC probe contains a D–π–A–π–D conjugated structure with a reactive CC double bond in the benzopyrylium moiety. In the presence of HSO3−, a nucleophilic addition reaction with the unsaturated carbon atom of XC occurred and rearranged the structure from the positively charged benzopyrylium moiety to neutral chromene. The HSO3−-induced nucleophilic addition product (XC-SO3) can be oxidized to the native XC, resulting in the reversible responses to HSO3−/H2O2 cycles. In the presence of HSO3−, XC presented a significant decrease in the absorption and emission spectra, as well as a solution colour change from blue to colourless under physiological conditions (pH = 7.4), which allows for the detection of HSO3− by the “naked eye”. By further incubation of XC-SO3 with H2O2, the spectroscopic and colour signals were recovered. Biologically relevant species including anions, reactive oxygen species (ROS), biothiols and cations induced negligible spectroscopic responses. The detection limits of XC for HSO3− and XC-SO3 for H2O2 were calculated to be 1.02 μM and 0.84 μM, respectively. XC has several advantages such as high selectivity, reliability at physiological pH and low cytotoxicity, which enable its application in biological samples. Fluorescence imaging experiments in live adult zebrafish and live nude mice demonstrated that XC has the potential to monitor the HSO3−/H2O2-regulated redox homeostasis in biosystems. The practical applications of XC were also demonstrated by the quantitative analysis of HSO3− in white wine and sugar samples.
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ACS Chemical Neuroscience
·
2021
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IF 4.418
Yishuai Yang,Yao Tan,Dongting Zhangsun,Xiaopeng Zhu,Sulan Luo
Nicotinic acetylcholine receptors (nAChRs) are essential pentameric ligand-gated ion channels that are distributed throughout the central and peripheral nervous systems and non-neuronal tissues in mammalian species that play critical roles in a variety of neural and mental activities. The α3β2 nAChR subtype participates in pain, addiction to nicotine, and other neurophysiological and pathological activities. Owing to the lack of highly selective pharmacological tools targeting α3β2, related research on its tissue distribution and function has been hindered. α-Conotoxin (α-CTx) LtIA, discovered from Conus literatus in our lab, potently and selectively blocks α3β2 nAChR, providing an important molecular probe to study the α3β2 nAChR structure and function. We used the fluorescent molecule 5-carboxytetramethylrhodamine succinimidyl ester, which can react with the N-terminus of LtIA, to obtain a novel fluorescent analogue of LtIA (LtIA-F). The potency and selectivity of LtIA-F were tested using a two-electrode voltage clamp recording on various nAChRs expressed in Xenopus laevis oocytes. LtIA-F potently inhibited ACh-evoked currents at the α3β2 nAChR, with an IC50 value of 90.66 nM, displaying a ∼4-fold decrease in potency compared with native LtIA without a change in selectivity. The serum stability results indicated that LtIA-F exhibited stability similar to that of native LtIA. This study on an α-CTx LtIA fluorescent analogue provides a wealth of pharmacological tools to explore the structure–function relationship, distribution, and ligand binding domain of the α3β2 nAChR subtype.
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Journal of Materials Chemistry B
·
2021
·Vol. 9
·期 41
·8659-8666
·
IF 6.331
Dan Fang,Ting Li,Ziyu Wu,Qi Wang,Mimi Wan,Min Zhou,Chun Mao
It is of great significance to find effective thrombolytic treatments due to the harm caused by thrombosis to human health. Based on the formation mechanism and complex microenvironment of a thrombus, polydopamine nanomotors (PDANMs) modified by the peptide of Arg–Gly–Asp (RGD) and loaded with urokinase (UK) were designed and prepared. A polydopamine (PDA) substrate has a good photothermal conversion effect. Under near-infrared (NIR) light irradiation, it can not only perform photothermal therapy (PTT) on thrombus, but also provide the driving force of PDANMs. Thrombolytic drug UK was loaded in the mesoporous structure of the PDA substrate and can be released at the thrombus site for drug therapy. The modified RGD can target the thrombus site, moreover, benefiting from the guanidine group of L-arginine in the peptide chain, and RGD can interact with reactive oxygen species (ROS) in the thrombus microenvironment to produce nitric oxide (NO). NO not only propelled the movement of nanomotors, but also promoted the growth of vascular endothelial cells to repair damaged blood vessels. The experimental results show that NIR and NO can provide dual driving sources for the nanosystem to achieve continuous and deep penetration of the drug-loaded nanomotors at the thrombus site, while realizing the photothermal and drug synergistic therapy to enhance the therapeutic effect and promote the growth of vascular endothelium cells. This kind of thrombus treatment strategy based on nanomotor drug delivery systems will provide good technical support for the clinical treatment of inferior vena cava thrombus.
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FOOD RESEARCH INTERNATIONAL
·
2021
·
IF 6.475
Zhiyong Xie,Yixuan Bai,Guijie Chen,Wei Dong,Yujia Peng,Weiqi Xu,Yi Sun,Xiaoxiong Zeng,Zhonghua Liu
Aspergillus cristatus is the dominant fungus involved in the fermentation of Fuzhuan brick tea (FBT). The intracellular polysaccharides (IPSs) from A. cristatus (MK346334, NCBI), isolated from FBT, exhibited immunomodulatory activity in vitro while the effects in vivo on immune system and gut microbiota remain unclear. In this study, IPSs and the purified fraction (IPSs-2) from IPSs were prepared and their immunomodulatory activities were investigated with cyclophosphamide (Cy)-induced immunosuppressive mice. As results, IPSs strengthened the immune function, manifesting in the improvement of body weight, daily intake, immune organ indices, cytokines and immunoglobulin. Meanwhile, IPSs attenuated Cy-induced intestinal barrier injury and promoted the expression of tight junction proteins and mucin, reinforcing the intestinal barrier function. Moreover, IPSs not only promoted the production of short-chain fatty acids and the expression of G protein-coupled receptor (GPR), but also balanced dysbiosis of gut microbiota through elevating the growth of beneficial bacteria while reducing pathobionts to maintain the homeostasis of the microbial ecology. These results suggested that IPSs exerted immunomodulatory activity linking with the restoration of intestinal barrier function and regulation of gut microbiota, which contributes to the development of novel probiotics and effective immunomodulators for strengthening host immunity and gut health.
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AAPS Journal
·
2021
·Vol. 24
·期 1
·1-13
·
IF 4.009
Zhao Xuan,Huang Chengyuan,Su Meiling,Ran Yu,Wang Ying,Yin Zongning
Celastrol (CLT) has shown anti-rheumatic activity against rheumatoid arthritis, while its poor water solubility and high organ toxicity restrict its further therapeutic applications. To mitigate these challenges, a reactive oxygen species (ROS)–responsive nanoparticle was developed for celastrol delivery based on the excessive ROS at the pathologic sites, which was synthesized by conjugating bilirubin to a polyethylene glycol (PEG) chain. The PEGylated bilirubin self-assembled into nanoparticle (BRNP) in aqueous solution had a hydrodynamic diameter of around 68.6 nm, and celastrol was loaded into BRNP (CLT/BRNP) with a drug encapsulation efficiency of 72.6% and a loading capacity of 6.6%. In vitro study revealed that CLT/BRNP exhibited the capacity of scavenging intracellular ROS and down-regulating the level of nitric oxide after it was effectively internalized by activated macrophages. Furthermore, in adjuvant-induced arthritis rats, BRNP was accumulated preferentially at inflamed joints, alleviating the joint swelling and bone erosion, which significantly decreased the secretion of pro-inflammatory cytokines to suppress the RA progression. Importantly, CLT/BRNP markedly enhanced its anti-arthritic effect and attenuated the toxic effect compared with free celastrol. Taken together, our results suggested that CLT/BRNP could be used for targeted drug delivery in rheumatoid arthritis. Graphical abstract
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危险品化学品经营许可证（带存储）